Unpacking ORBITA: What the Controversial Stent Study Really Means

November 20, 2017
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Lumere

Recently published results from the ORBITA trial call into question whether percutaneous coronary intervention (PCI) is actually effective at reducing angina, or whether the reduction in chest pain associated with the procedure is purely due to the placebo effect. Below, Lumere experts Elizabeth Nee and Erin Gavin, PharmD, look past the headlines and hand wringing.

Why did the results of this trial hit such a nerve, particularly in the lay press?

Elizabeth: The ORBITA trial is especially provocative because it represents the first sham trial of PCI in 40+ years. Patients were randomized to receive either a drug-eluting stent or a sham procedure that mimicked implantation of a stent.

In this patient population with stable coronary artery disease (CAD), previous randomized controlled trials that did not involve a sham procedure had shown that PCI did not reduce mortality or prevent myocardial infarctions (MI) compared to optimal medical therapy. The case for PCI in these patients was subsequently limited to symptomatic relief.

We should note that this trial was limited to patients with single-vessel stable CAD, and did not study unstable or post-MI patients (where there is stronger support for PCI). Also, the evaluation timeframe was only six weeks, which begs the question, would the placebo effect have continued?

Does this trial make a case for sham studies?

Elizabeth: Hopefully this study will open the door to more sham trials, especially in cardiology. There would be benefit in studying device procedures with relatively low levels of response, especially in instances when drug therapy alone might produce the desired response; for example, ablation for atrial fibrillation or even cardiac resynchronization therapy.

Speaking of drug therapy, how did medication use compare to current practice?

Erin: The ORBITA trial included a six-week period of medication optimization between enrollment and randomization. The focus was to have each patient on at least two anti-anginal therapies, which is appropriate and consistent with clinical guidelines. However, the rate of therapy titration and frequent access to a cardiologist doesn’t reflect real-world patient or provider experience.

Did this affect the trial outcomes?

Erin: Because of the aggressive treatment approach, 11% of the final study population was randomized after becoming asymptomatic, meaning they were less likely to benefit from PCI.

It’s also worth noting that the proportion of patients who were asymptomatic or only had symptoms with strenuous exercise increased from 2.5% to 23.5% on drug therapy alone. Therefore, it is hardly surprising that there was no significant difference between groups in measures of symptom improvement and quality of life.

What will be ORBITA‘s long-term impact?

Elizabeth: We’re already seeing a lot of pushback from interventional cardiologists who’ve long relied on PCI, so I don’t expect any immediate changes to the guidelines. It may be difficult to get approval for a larger or longer trial on ethical grounds, at least in the United States.

Erin: For many patients in this trial, symptom improvement was accomplished simply by optimizing medication therapy. This should encourage cardiologists to give extra consideration to drug therapy before moving to more invasive procedures such as PCI.

Like Erin and Elizabeth, many of Lumere’s experts have hands-on clinical, pharmaceutical or device design experience. Our team will continue to monitor for updates and apprise our clients of developments.

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